Modern treatment methods have led to major improvements in the survival rate of children with Wilms' tumor (WT). Combined therapy using surgery, radiation therapy and chemotherapy now cures 90% of patients with favorable histology WT. Those with renal tumors of unfavorable histology, especially those with metastases, either synchronous or metachronous, are at higher risk. Their survival is in the 50-65% range, and better treatments clearly are needed. At the same time, all therapies have their associated risks and complications, and some are costly and burdensome for the medical staff and the family. Refinements of therapy for children with a good outlook are therefore needed to increase efficiency, and reduce risks and costs. NWTS-4 is designed to achieve these objectives through better understanding of the renal tumors of childhood, their epidemiology and the late effects of successful therapy, while conducting clinical trials of novel therapies. These trials address the following question: Can single daily doses of effective chemotherapeutic agents given more frequently over a shorter interval improve the outlook while decreasing costs and family stress? The NWTS thus has undertaken a new task: the reduction of the socioeconomic burdens of therapy while continuing to strive for more cures and continuing its pioneering studies of the delayed consequences of Wilms' tumor treatments.